Safety, tolerability, and preliminary efficacy results in patients with advanced gastric/gastroesophageal junction adenocarcinoma from a phase Ib/II study of CLDN18.2 CAR T-cell therapy (CT041).
Authors: Changsong QI, Chang Liu, Jifang Gong, Jian Li, Dan Liu, Sai Ge, Miao Zhang, Zhi Peng, Jun Zhou, Xiaotian Zhang, Ji Zheng, Jun Xiao, Daijing Yuan, Yueying Peng, Huamao Wang, Zonghai Li, Lin Shen
Journal: Journal of Clinical Oncology (2022)

4017 Background: Claudin18.2 (CLDN18.2) has emerged as a promising therapeutic target, which is normally confined to gastric mucosa tight junctions but is often expressed in gastric/gastroesophageal junction (G/GEJ) cancer. CT041, an CLDN18.2-redirected CAR T-cell therapy, showed promising anti-tumor activity in preclinical studies (Hua J. J Natl Cancer Inst. 2019). Recently reported results of a phase I study (Qi C. Ann. Oncol 2021) showed that CT041 was well tolerated and had encouraging efficacy in previously treated patients with CLDN18.2-positive advanced G/GEJ cancer. Here we report the preliminary safety and efficacy data on patients with G/GEJ cancer in an ongoing phase Ib/II study (CT041-ST-01, NCT04581473). Methods: This open-label, 2-part, multicenter, phase Ib/II study was conducted to assess the safety, tolerability and efficacy of CT041 in patients with previously treated, CLDN18.2-positive advanced G/GEJ cancer. The study consisted of a dose escalation/dose-expansion phase (phase Ib) and a safety/efficacy confirmatory phase (phase II). In the dose escalation/de-escalation phase, CT041 dose levels of 2.5 × 10 8 and 3.75 × 10 8 were investigated using 3 + 3 design. The primary objective of the phase Ib part was to determine the safety, tolerability and recommended phase 2 dose (RP2D) of CT041. Data are reported as of December 22, 2021. Results: From November 2020 to May 2021,14 eligible patients with G/GEJ cancer were enrolled in phase Ib. The median (range) age was 44.5 (23-71); 85.7% had received 2 prior lines of treatment and 14.3% had at least 3 lines; 57.1% had ≥ 3 metastatic organs, with 92.9% had peritoneal dissemination; 64.3% had signet ring cell carcinoma. Among them, 3 received 3.75 × 10 8 and 11 received 2.5 × 10 8 dose level with up to 3 doses, respectively. Most commonly reported AEs of grade 3 or higher were hematologic toxicity related with lymphodepletion. There were no dose-limiting toxicities, treatment-related death, neurologic toxicity (ICANS) or gastrointestinal toxicities observed. Most CRS were grade 1 or 2, and only one patient experienced grade 4 CRS and fully recovered. As of the data cut-off, 8 of 14 (57.1%) patients achieved partial response (PR); 2 of 14 (14.3%) patients showed stable disease (SD) . With a median follow-up time of 8.9 months (95%CI 5.91, NE), the median progression-free survival (PFS) was 5.6 months (95%CI 1.9, 7.4), and median overall survival (OS) was 10.8 months (95%CI 5.1, NE) with 7 patients still alive at last follow-up. Conclusions: These preliminary results suggest that CT041 had manageable safety/tolerability profile and promising efficacy in patients with previously treated advanced G/GEJ cancer. This study is ongoing with further investigation of CT041 in phase II underway. Clinical trial information: NCT04581473.